A multicenter phase II randomized trial of durvalumab (D) versus physician’s choice chemotherapy (PCC) in patients (pts) with recurrent ovarian clear cell adenocarcinoma (MOCCA/APGOT-OV2/GCGS-OV3).
Authors: David Shao Peng Tan, Chel Hun Choi, Natalie Ngoi, Haoyang Sun, Valerie Heong, Samuel Guan Wei Ow, Wen Yee Chay, Hee Seung Kim, Yi Wan Lim, Geraldine Goss, Jeffrey C. Goh, Vilianty Luo, Bee Choo Tai, Diana Lim, Nivashini Kaliaperumal, Veonice Bijin AU, John Connolly, Jae-Weon Kim, Michael Friedlander, Kidong Kim
Journal: Journal of Clinical Oncology (2022)

5565 Background: The optimal treatment of recurrent ovarian clear cell carcinoma (rOCCC) remains unknown. Prior data suggests rOCCC is a chemo-resistant disease that may respond to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibition (ICI). We aimed to determine the efficacy of D versus PCC in pts with rOCCC. Methods: In this multicentre, open-label, randomised phase 2 trial, 9 academic centres across Singapore, South Korea and Australia, enrolled rOCCC (determined histologically) and Eastern Cooperative Oncology Group performance status (PS) 0-2 pts, who had recurred after prior platinum-based chemotherapy and had not received more than 4 prior lines of systemic therapy, nor prior ICI therapy. Eligible pts were randomly assigned (2:1), using dynamic block randomization with block size of 6, and stratification by ECOG PS, to receive D (1500mg on day 1, in 28-day cycles) or PCC until disease progression (PD), intolerable toxicity or withdrawal of consent. Pts with PD on PCC were allowed to crossover to D. The primary endpoint was investigator-assessed progression-free survival (PFS) by RECIST version 1.1 and analyses included pts who had commenced at least 1 cycle of study treatment. Results: Between 7 Nov 2017 and 17 Feb 2020, 57 pts were assessed for eligibility, of whom 47 (PS 0-1) were randomly assigned to treatment with D (31 pts) or PCC (16 pts). At the data cut-off date (10 Jan 2022), the median follow-up was 83.0 weeks (IQR: 54.1—97.0) in the PCC group and 107.0 weeks (IQR: 82.7—116.4) in the D group. Median PFS was 7.4 weeks (IQR: 6.0—16.0) in the D group and 14.0 (IQR: 7.0—28.6) in the PCC group (HR 1.5 [95% CI 0.8-2.8], log-rank p = 0.89). The objective response rate (ORR) was 10.7% in pts randomised to D and 18.8% in the PCC group (p = 0.884). Clinical benefit rate (CR/PR/SD for ≥16weeks) was similar for PCC (37.5%) and D (32.1%) (p = 0.756). 9 pts on PCC crossed over to receive D, with 2 of the 8 evaluable pts achieving partial response (PR). When crossover D pts were included, ORR to D was 13.9% (5/36) with a clinical benefit rate of 30.6% (11/36). Median duration of response was 44 weeks for the 3 PCC responders (PR to gemcitabine 24.9wks, PR to liposomal doxorubicin 65.7wks, CR to carboplatin/liposomal doxorubicin 44wks), and 18 weeks (range 2.1-45.3) for the 5 responders to D. Frequency of adverse events (AEs) across all grades was 68.8% for PCC and 38.7% for D. Grade 3/4 AEs were observed in 37.5% of PCC pts and 9.7% of D pts. Conclusions: No significant differences in PFS, ORR or clinical benefit rate were observed between D and PCC treatment in rOCCC. Treatment with D was associated with less grade 3-4 adverse events. Correlative translational analyses to elucidate predictive biomarkers of response and resistance are ongoing. Clinical trial information: NCT03405454.